Cycloheximide, C.sub.15 H.sub.23 NO.sub.4, beta-[2-(3,5-dimethyl-2-oxocyclohexyl)-2-hydroxyethyl]glutarimide, is now a well-known fungicide. Whiffen, et al., U.S. Pat. No. 2,574,519, issued in 1951, describes it and claims a process for its production. Cycloheximide is water soluble, active at very low concentrations against a variety of agriculturally significant fungus organisms, and is not stable in basic media or in combination with a variety of other agriculturally active components. Numerous patents have issued in the United States and elsewhere and publications are prevalent describing and claiming various ideas and attempts to stabilize cycloheximide or to prepare derivatives of cycloheximide so that its useful life could be extended for broader fungicide applications.
A few representative United States patents evidencing that type of prior art work include:
______________________________________ Klomparens/Vellaire U.S. 2,871,155 Murray U.S. 2,894,872 Murray U.S. 2,894,871 Vellaire U.S. 3,014,840 and Schroeter/Bojack U.S. 3,092,546 ______________________________________
and others listed in an accompanying prior art statement. However, this invention is not concerned directly with stabilization of cycloheximide, but rather is directed toward providing a controlled release form of cycloheximide which extends the field life of cycloheximide as a useful fungicide where cycloheximide would be useful for combatting fungi in farm crop areas, in the presence or absence of agriculturally significant growing crops.
Prior attempts at control release of cycloheximide have included the use of cycloheximide (CHI) impregnated clay granules coated with hydrophobic materials. Such formulations do not provide adequate control of CHI, possibly due to an incomplete coat of the CHI-impregnated granule. The incompleteness or non-uniformity of the hydrophobic coating could be affected by air temperature, air movement, humidity, spray time, blender efficiency of the coating equipment, or to the lack of personnel expertise. Other attempts at controlled release of active ingredients have included the mixing of active materials, including aspirin, drugs, ascorbic acid with polyethylene glycol of 6000-7500 molecular weight range in a chlorinated, non-polar solvent, and then removing the chlorinated, non-polar solvent, e.g., by evaporation. See Gakenheimer U.S. Pat. No. 2,540,253 and DeLange, et al., U.S. Pat. No. 3,679,797. Such methods and compositions require providing equipment for the removal and recovery of huge quantities of organic solvent.
Prior patents such as U.S. Pat. No. 2,977,282 have suggested mixing plant disease antibiotics, including CHI, as aqueous solutions of antibiotics with polyhydroxy alcohols to increase the rate of absorption of the antibiotic, e.g., CHI, by the plant, thereby hopefully reducing chances of fungus disease. However, such compositions involve the use of aqueous solutions which are disadvantageous for the stable, controlled release use of CHI.
Allan, U.S. Pat. No. 3,813,236 discloses sustained release pesticide compositions involving the chemical combination of the active pesticide with an inert natural polymer (wood derivatives) such as lignin or lignin containing material such as tree bark. When exposed to environmental conditions, the chemical bond between the natural polymer and pesticide is broken by hydrolysis to yield the pesticide over an extended period of time. However, with CHI, it is preferred to avoid chemical reaction of the active ingredient, CHI, with diluents, coating agents, and carriers with which it is combined, because CHI is inherently somewhat unstable in the presence of other reactive materials. Moreover, cycloheximide has already been combined with solubilized lignin to reduce its phytotoxicity (See Klomparens, et al., U.S. Pat. No. 2,871,155), but broader and different, non-liquid methods are sought for the controlled release of CHI.
Also, Muramata, et al., U.S. Pat. No. 3,980,463 discloses a process for making granular compositions of specific size distribution range by adding solutions of active ingredients and a binder to a carrier of defined size ranges. The binder can be materials such as lignin sulfonate, carboxymethyl cellulose, polyvinyl alcohol, starch, sodium alginate, an acrylic resin, rosin, a coumarone resin, a petroleum resin, shellac and gelatin, and are dispersed in aqueous or organic liquid solvents. However, such compositions involve the use of liquid solvents which must be removed from the granular product by evaporation or otherwise.
However, by this invention there is provided an inexpensive way to provide controlled release of a water-soluble agricultural drug, CHI, which, to our knowledge, has not been done before or at least has not been published. The purpose and objects of this invention are to provide a controlled release form of CHI which is triggered by moisture over a wide range of environmental (moisture) conditions. The controlled release system of this invention will accommodate a range of CHI release rates, varying from a few minutes to several weeks. This CHI controlled release system is adaptable for adjustment to provide varying CHI release rates for many different argicultural and rodent repellant types of applications, with small or large carrier granule sizes, and this system can be applied to any fungus-susceptible surface than can be sprayed, coated, dipped, mixed with the controlled release compositions.
In summary, it is an object of this invention to provide inexpensive, controlled release compositions of CHI which are adaptable for use in a variety of application uses and which are triggered by environmental moisture to provide CHI as needed in particular applications.
Other objects and advantages of this invention will be apparent to a person in the art from the remaining specification and the appended claims.